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Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS
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SYSNO ASEP 0560826 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS Author(s) Petrová, V. (GB)
Pearson, C.S. (US)
Ching, J. (GB)
Tribble, J.R. (SE)
Solano, A.G. (US)
Yang, Y. (GB)
Love, F.M. (GB)
Watt, R.J. (GB)
Osborne, A. (GB)
Reid, A. (GB)
Williams, P.A. (SE)
Martin, K.R. (GB)
Geller, H.M. (US)
Eva, R. (GB)
Fawcett, James (UEM-P) ORCIDArticle number 5614 Source Title Nature Communications. - : Nature Publishing Group
Roč. 11, č. 1 (2020)Number of pages 15 s. Language eng - English Country GB - United Kingdom Keywords spinal-cord ; growth cone ; phosphoinositides ; transport ; outgrowth OECD category Neurosciences (including psychophysiology R&D Projects EF15_003/0000419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 000612233600024 EID SCOPUS 85095418690 DOI 10.1038/s41467-020-19436-y Annotation Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin's endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2023 Electronic address https://www.nature.com/articles/s41467-020-19436-y
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